Associations between white matter microstructure and cognitive decline in major depressive disorder versus controls in Germany: a prospective case-control cohort study
Kira Flinkenflügel, Susanne Meinert, Christopher Hirtsiefer, Dominik Grotegerd, Marius Gruber, Janik Goltermann, Nils R. Winter, Frederike Stein, Katharina Brosch, Elisabeth J. Leehr, Joscha Böhnlein, Katharina Dohm, Jochen Bauer, Ronny Redlich, Tim Hahn, Jonathan Repple, Nils Opel, Robert Nitsch, Hamidreza Jamalabadi, Benjamin Straube, Nina Alexander, Andreas Jansen, Igor Nenadić, Martijn P. van den Heuvel, Katharina Thiel, Alexandra Winter, Florian Thomas-Odenthal, Paula Usemann, Lea Teutenberg, Julia-Katharina Pfarr, Tilo Kircher, Udo Dannlowski
Abstract
BACKGROUND: Cognitive deficits are a key source of disability in individuals with major depressive disorder (MDD) and worsen with disease progression. Despite their clinical relevance, the underlying mechanisms of cognitive deficits remain poorly elucidated, hampering effective treatment strategies. Emerging evidence suggests that alterations in white matter microstructure might contribute to cognitive dysfunction in MDD. We aimed to investigate the complex association between changes in white matter integrity, cognitive decline, and disease course in MDD in a comprehensive longitudinal dataset. METHODS: ) following the Nakagawa and Schielzeth method to quantify explained variance. The association between changes in cognitive performance and changes in white matter integrity was analysed. Finally, we examined whether the depressive disease course between assessments predicted cognitive performance at follow-up and whether white matter integrity mediated this association. People with lived experience were not involved in the research and writing process. FINDINGS: =0·004). In participants with MDD, changes in white matter integrity (p=0·0040, β=0·071) and adverse depressive disease course (p=0·0022, β=-0·073) independently predicted lower cognitive performance at follow-up. INTERPRETATION: Alterations of white matter integrity occurred over time to a greater extent in participants with MDD than in healthy controls, and decline in white matter integrity was associated with a decline in cognitive performance across groups. Our findings emphasise the crucial role of white matter microstructure and disease progression in depression-related cognitive dysfunction, making both priority targets for future treatment development. FUNDING: German Research Foundation (DFG).